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Development of Biochemical Profile of Novel Bigenic Mice AD Models

  • Author(s): Arner, Andrew Michael
  • Advisor(s): Rissman, Robert
  • et al.
Abstract

Tauopathies encompass several of the most prevalent neurodegenerative diseases that consistently progress to severe dementia and motor impairments. They involve tau hyperphosphorylation, which leads to the proteins detachment from associated microtubules, and a decline in the structural integrity of the cytoskeleton. This disassociation is followed by intracellular tau aggregation that causes impairment of axonal function. The most common tauopathy, Alzheimer disease (AD), affects 5 million individuals in the United States alone. Due to a lack of understanding of the pathology involved in AD, treatment is currently limited to minimizing symptoms, without the ability to slow the rate of neurodegeneration. Another component of AD is that it is uniquely associated with extracellular accumulation of amyloid beta plaques, which appear to disrupt synaptic function, as well as induce inflammation. Developing and researching a variety of transgenic animals meant to model these diseases is critical to advancing the efficacy of their treatment and prevention. A line of transgenic mice containing the human amyloid precursor protein gene (hAPP) was bred with a recently generated line of mice that overexpress a variant of the human triple repeat tau gene, to create a novel bigenic line of mice that model AD. A biochemical and cognitive profile was developed for both young and aged mice with these three differing transgenic genotypes, along with a control group of non-transgenic mice.

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